Work in this laboratory has been concentrated on the mechanism of histone acetylation. It appears that acetylation of histones is accomplished by transfer of acetate from acetyl-CoA to histone amino groups. Various laboratories have reported on histone acetyl transferase activity in nuclei, but work in this laboratory has pinpointed this type of activity in the chromatin itself. Recently, we have succeeded in extracting this enzyme activity from the chromatin, using a procedure similar to that used for the extraction of RNA- polymerase activity from eukaryotic chromatin. We propose to investigate the purified enzyme thoroughly, as to its specificity and kinetic properties. Since the relative pattern of acetylation of the various histone fractions in vivo and even in chromatin in vitro, differs from that of free histones in the presence of the enzyme extract, structural studies will be carried out on the effect on histone acetyl transferase activity of addition of purifed DNA and synthetic polymers to the free histones. It seems important to learn more about this enzyme which may be the target of various regulatory influences in the cell nucleus which may be involved in differentiation.